Another variant of the magnetographic technique is the measurement of fluid flow inside an object, if the flow has a component in the direction of a magnetic field gradient. A signal induced in a volume of flowing liquid will appear downstream at later times. In blood for example, a water proton signal persists for several tenths of a second, and should be detectable for some distance along a blood vessel, permitting simultaneous measurement of volumes, directions, and rates of flow within the blood vessels.
Instrumentation
The basic instrumentation required for magnetography consists of a magnet, coils for generating constant or pulsed magnetic field gradients, a pulsed or CW NMR spectrometer (simple experiments are possible with a CW spectrometer, but the more sophisticated applications require a pulsed instrument), a small computer for digital data processing, a magnetic tape unit or equivalent for data storage, and one or more output display devices for presentation of the images.
(Method Claims) 3/10/72
1. A magnetic resonance technique comprising:
(A) providing an object within which is contained a spatial distribution of magnetically susceptible entities having properties which depend upon the magnetic field at the locations of the entities,
(B) subjecting the entities to a directional magnetic field which varies in a known way through a selected volume of the object containing a spatial distribution of the entities,
(C) applying electro-magnetic energy to the entities in a manner to excite the entities to resonance at frequencies corresponding to their locations in the magnetic field gradient,
(D) detecting the resonance signals thus induced to provide signals indicative of the spatial distribution across the gradient of those entities exhibiting like magnetically dependent properties.
2. The technique as defined in claim 1 wherein the magnetic field is varied directionally.
3. The technique as defined in claim 1 wherein the magnetic field is varied in magnitude.
4. The technique as defined in claim 1 wherein the entities are nuclei.
5. The technique as defined in claim 1 wherein the entities are electrons.
6. The technique as defined in claim 1 wherein the electromagnetic energy is applied as continuous wave energy.
7. The technique as defined in claim 2 wherein the electromagnetic energy is applied in discrete pulses.
8. The technique as defined in claim 1 including the further steps of
(A) changing the angle of orientation between the object and the magnetic field, and
(B) repeating steps (c) and (d) of claim 1 at least once.
9. The technique as defined in claim 8 including:
(A) storing the signals generated until completion of the steps of claim 8, and
(B) subjecting the stored signals to an imaging process to produce a resultant image which is a two-dimensional projection of the object.
10. The technique as defined in claim 1 wherein the entities are nuclei and the electromagnetic energy is continuous wave applied at a first power level, and the additional steps of
(A) repeating the stems of claim 1 at a second power level, the first and second power levels being selected such as to effect signal saturation at one power level relative to the other, and
(B) observing the difference in the signals resulting from each of the power levels whereby the nuclei in different parts of the object may be distinguished.
11. The technique as defined in claim 1 wherein the entities are nuclei contained within a flexible medium and wherein
(A) the electromagnetic energy is applied in r.f. pulses, including
(1) applying a first pulse to a first region of the medium containing the nuclei to condition the nuclei therein to a first condition of magnetization,
(2) applying a second pulse to the first region to neutralize the first condition of magnetization of previously magnetized nuclei remaining therein, the second pulse being applied after the first at a time short with respect to the transverse relaxation time T2 of the conditioned nuclei, and
(B) detecting the nuclear induction signals at a second region within the magnetic field gradient from nuclei which had been subjected to the first pulse but not the second, whereby the detected signals are indicative of the flow rate of the nuclei and of the first region.
(Apparatus claims)
12. Magnetic resonance apparatus comprising:
(A) a means for selectively applying electromagnetic energy to an object containing a spatial distribution of magnetically susceptible entities,
(B) means for selectively applying a polarizing magnetic field to the object such that different ones of the distributed entities are subjected to predetermined magnetic fields of different magnitudes, the application of the electromagnetic energy and magnetic field being such as to excite the entities to resonance and produce a set of signals indicative of their magnetically dependent properties,
(C) means for detecting the resonance signals so produced, and
(D) means for displaying the signals in a manner to indicate a single planar projection of the spatial distribution of the entities and their magnetically dependent properties.
13. Apparatus as defined in claim 12 including
(A) means for re-orienting the directional relationship amongst the object, the applied electromagnetic energy and the magnetic field in a manner such as to excite the entities to resonance to produce a second set of signals in accordance with the re-oriented relationship, and
(B) means for combining the two sets of signals to produce a resultant set indicative of a two planar projection of the spatial distribution of the entities and their magnetically dependent properties.
14. Apparatus as defined in claim 12 including
(A) means for selectively re-orienting the directional relationship amongst the entities, the applied electromagnetic field and the polarizing magnetic field in a manner such as to excite the entities to produce a set of signals in accordance with each such re-oriented relationship, and
(B) means for combining the sets of signals to produce a resultant set indicative of a multiplanar projection of the spatial distribution of the entities and their magnetically dependent properties.
15. Apparatus as defined in claim 14 wherein the combining means includes
(A) computer means for accepting the detected signals storing them and adapting them for display by the display means, and
(B) wherein the re-orienting means includes control means operatively connected to the computer means for synchronizing the operations of the re-orienting means with the operations of the computer means.
16. Apparatus as defined in claim 15 wherein the signals are nuclear induction signals and the computer means includes means for computing the Fourier transform of the signals.
17. Apparatus as defined in claim ___ wherein the means for [something] applying [something] includes means for selectively applying r.f. pulses.
Notes
Chapter 1
1. Raymond Damadian, “Tumor Detection by Nuclear Magnetic Resonance,” Science 171, no. 3976 (March 1971): 1151–1153.
2. Paul C. Lauterbur, “One Path Out of Many: How MRI Actually Began,” in Encyclopedia of Magnetic Resonance, vol. 1, ed. David M. Grant and Robin K. Harris (Chichester, UK: John Wiley and Sons, 1996), 445–449.
3. Ibid.
4. Paul C. Lauterbur Collection, Chemical Heritage Foundation Archives, Philadelphia, PA.
5. Paul C. Lauterbur Collection, Chemical Heritage Foundation Archives, Philadelphia, PA. Hand-written notes on a yellow pad. There is no date, but it must be between 2000 and 2003, from the type of paper used.
6. The original notebook is in the Paul C. Lauterbur Collection, Chemical Heritage Foundation Archives, Philadelphia, PA.
7. Paul’s hand-written memorandum: “Recently there has been a suggestion that the concept of selective excitation of a spin system in a field gradient is in contradiction to even the most superficial implications of the uncertainty princip
le. This conclusion was based upon an analogy between the NMR response of a sample and linear response theory as pertains to an electronic circuit. It is our belief that the analogy is inadequate as it leads to the incorrect conclusions.”
8. Letter on the occasion of Paul’s 70th Birthday Celebration Symposium, “Zeugmatography and Beyond,” September 17–18, Beckman Institute, University of Illinois at Urbana-Champaign, now in the Paul C. Lauterbur Collection, Chemical Foundation Archives, Philadelphia, PA.
9. Hal Swartz, “Some of My Interactions with Paul C. Lauterbur,” EPR News Letter: The Publication of the International EPR (ESR) Society, vol. 14, nos. 1–2 (2004): 7–8.
10. Jeff Baird, “Alpha Delta Alumnus Paul Lauterbur’s Research Led to MRI Technology, Now Used in Millions of Medical Investigations Worldwide,” The Laurel of Phi Kappa Tau, Winter 2004, 33–39.
Chapter 2
1. Paul C. Lauterbur, “To Think, To Do, To Believe,” in Kyoto Prizes and Inamori Grants, 1994 (Kyoto: Inamori Foundation, 1995).
2. The Kyoto Prizes were established by Kazuo Inamori as one of the works of the Inamori Foundation, which he founded in 1984. Dr. Inamori founded the Kyocera Corporation in 1959, manufacturing ceramic materials used in such areas as electronic ceramics, engineering ceramics, and structural ceramics, and built it into a highly profitable international organization. In keeping with Dr. Inamori’s concern for balance among scientific achievements and psychological maturity, three prizes were instituted, in advanced technology, basic sciences, and creative arts and moral sciences. Paul Lauterbur was the recipient of the Kyoto Prize in Advanced Technology in 1994, the tenth anniversary of the establishment of the prizes.
3. Lauterbur, “To Think, To Do, To Believe.”
4. The Yellow Jacket: Year Book of Sidney High School, Class of 1947, Sidney, Ohio, p. 14.
5. Shearl Edler, “The Spirit of the 76th,” Sidney Daily News, Special Commemorative Supplement, April 21, 2004.
6. Personal communication, Roger McDermott, Harold McDermott’s son.
7. Henry De Wolf Smyth, Atomic Energy for Military Purposes: The Official Report on the Development of the Atomic Bomb under the Auspices of the United States Government, 1940–1945 (Princeton, NJ: Princeton University Press, 1945).
Chapter 3
1. Irvin M. Krieger, comments in The Case Chemist (Department of Chemistry, Case Western Reserve University), Fall 2003, no. 99.
2. Paul received the Medal of Honor of the Institute of Electrical and Electronics Engineers in 1987.
3. This was Quienke’s method for determining magnetic susceptibility.
4. Krieger, comments in The Case Chemist.
5. Hexaphenyl ethane (six benzene rings attached to a two-carbon unit) splits easily into two triphenylmethanes (i.e., the carbon bond splits, yielding two of the one-carbon units, each carrying three benzene rings), while hexaphenyl disiloethane (in which the C–C ethane bond is replaced by a Si–Si bond) is extremely stable.
6. Paul C. Lauterbur, “An Attempted Preparation of (Triphenylmethyl) Triphenysilane,” bachelor’s thesis, Case Institute of Technology, 1951. Triphenylsilane has three benzene rings attached to a silicon molecule. The free radical means it contains an unpaired electron; it was suspected that free radicals might affect the characteristics of rubber. Paul attempted to synthesize the organosilicon free radical, triphenylsilane, or its reaction products.
7. F. S. Kipping, who first made silicones, thought Si–Si–Si was Si=O, and named it silicone to be analogous with ketones.
8. It is larger and can make two more bonds than carbon. The bonds are more open to attack by water because, with their n orbitals, silicon atoms are farther from their partners. The C–Cl bonds are very stable, but Si–Cl bonds are hydrolyzed (broken up in water) in a shot. SiF has the most stable of silicon bonds, but it won’t stay together in water. Si doesn’t readily make double bonds because the bigger orbitals of two Si atoms are father apart.
9. Earl L. Warrick, Forty Years of Firsts: The Recollections of a Dow Corning Pioneer (New York: McGraw-Hill, 1990), 28.
10. Ibid.
11. Paul C. Lauterbur, “Autobiography” (Nobel Foundation, 2003), http://www.nobelprize.org/nobel_prizes/medicine/laureates/2003/lauterbur-autobio.html.
12. Earl L. Warrick and Paul C. Lauterbur, “Filler Phenomena in Silicon Rubber,” Industrial & Engineering Chemistry 47, no. 3 (March 1955): 486–491.
13. Warren G. Proctor and Fuchun Yu, “The Dependence of Nuclear Magnetic Frequency upon a Chemical Compound,” Physical Review 77, no. 5 (March 1950): 717.
14. Jiri Jonas and Charles P. Slichter, “Herbert Sander Gutowsky,” in Biographical Memoirs, vol. 88, ed. National Academy of Sciences (Washington, DC: National Academies Press, 2006).
15. Cindy Gill, “Magnetic Personality,” Pitt Magazine (University of Pittsburgh), Fall 2004, 14–18.
16. Paul C. Lauterbur, “To Think, To Do, To Believe,” in Kyoto Prizes and Inamori Grants, 1994 (Kyoto: Inamori Foundation, 1995).
17. Austin Elliott, “From Magnetic Moments to Medical Imaging,” Physiology News, Summer 2004.
18. Gill, “Magnetic Personality.”
19. Valerie G. Rankow, “Paul Lauterbur: ‘Superb One-on-One Teacher,’” Village Times Herald, December 27, 1984.
20. Austin Elliott, “Interview with Paul Lauterbur, December 2003,” Physiology News, Summer 2004.
21. A Varian 40 MHz NMR spectrometer.
22. These were an early study of 31P NMR, an early survey of 19F NMR, a study of 11B, and the first analysis of an AB4NMR spectrum.
Chapter 4
1. Other factors, such as spin number, also contribute.
2. The method was N pure quadrupole resonance (NQR).
3. Infrared spectroscopy measures the frequencies of a molecule’s vibrations, which depend on the masses of the atoms and the strengths of chemical bonds. Studies of the IR spectra of a vast number of substances demonstrated that vibrational frequencies correlate well with many details of molecular structure.
4. This was a Varian magnet resonating at 40 MHz for protons. The machine was capable of observing 13C at 8.5 MHz frequency and 10,000 gauss magnetic field strength (1 Tesla, in modern units).
5. The transmitter coil had been plugged into the receiver coil, and vice versa.
6. He used an 8.5 Mc/s RF unit.
7. G. R. Holzman, Paul C. Lauterbur, John H. Anderson, and W. Koth, “Nuclear Magnetic Resonance Field Shifts of Si29 in Various Materials,” Journal of Chemical Physics 25, no. 1 (July 1956): 172–173.
8. For example, the rapid passage technique was used.
9. Charles H. Holm, “Observation of Chemical Shielding and Spin Coupling of C13 Nuclei in Various Chemical Compounds by Nuclear Magnetic Resonance,” Journal of Chemical Physics 26, no. 4 (March 1957): 707–708; Paul C. Lauterbur, “C13 Nuclear Magnetic Resonance Spectra,” Journal of Chemical Physics 26, no. 1 (January 1957): 217–218.
10. All of this was done at 8.5 MHz (Paul lowered the field so that 13C would resonate at 740 MHz for 1H at a field of 8,000 gauss.) The RF unit was a single frequency, so if you could move the field, you could do some experiments without buying another RF unit.
11. Methyl iodide has four carbon peaks, and therefore provided an internal frequency scale.
12. Paul used the dispersion mode rather than the normal absorption mode in order to use high RF power to detect the weak signal without saturating it. Al Redfield, a few years earlier, while he was a postdoctoral student with Nicholaas Bloembergen at Harvard, discovered that the absorption mode signal saturated as expected with increasing RF power, but the dispersion mode was much more difficult to saturate. Out of this work Redfield developed a theory of spin temperature in the rotating frame. The theory has had a profound effect on the use of NMR in solids, as well as in the development of 13C NMR. But while this increased the size of the signals, it also broadened them to the point that at first, some people thought they were hardly worthwhile.
13. The is
sue was the degree to which the atomic nuclei of carbon and hydrogen interact and affect each other’s magnetic characteristics; this is called the coupling constant, an important parameter in NMR studies and a number that must be known to understand the magnetic characteristics of a molecule.
14. Christine Des Garennes, “2003 Nobel Laureate Dies at Urbana Home,” The News-Gazette, March 28, 2007.
15. A breakthrough in studying 13C NMR (which applied in many respects to other nuclei of low sensitivity such as 15N) was the adroit use of proton spin decoupling. At the Third Conference on Experimental Aspects of NMR Spectroscopy, held in Pittsburgh in 1962, Lauterbur, Grant, and Schoolery independently announced enhancements of the signal-to-noise ratio in 13C NMR spectra obtained by double irradiation. Lauterbur and Yajko observed an enhancement of S/N in a proton-decoupling experiment which exceeded that normally expected from the simple collapse of the proton-coupling multiplets, an early indication of the nuclear Overhauser effect in 13C NMR.
16. Super conducting magnets and Fourier Transform NMR.
Ray was later a Varian Associates representative in Europe.
17. An outside reader is someone from outside the university who is a member of the examination committee that awards the PhD.
Paul Lauterbur and the Invention of MRI Page 23